The present commercially available canine Bordetella bronchiseptica vaccine product is composed of an inactivated, nonadjuvanted Bordetella bronchiseptica whole cell bacterin. Such whole cell bacterin can lead to cell protein related post-vaccination reactions. The p68 protein of B. bronchiseptica is antigenically similar to the Outer Membrane Protein (OMP) of B. pertussis and the OMP of B. parapertussis (Shahin et al., “Characterization of the Protective Capacity and Immunogenicity of the 69-kD Outer Membrane Protein of Bordetella pertussis”, J. Exp. Med., 171: 63-73, 1990). A protective role of this OMP has been demonstrated for mice (Shahin et al., supra; Novotny et al., “Biologic and Protective Properties of the 69-kD Outer Membrane Protein of Bordetella pertussis: A Novel Formulation for a Acellular Pertussis Vaccine”, J. Infect. Dis. 164:114-22, 1991), humans (He et al., “Protective Role of Immunoglobulin G Antibodies to Filamentous Hemagglutinin and Pertactin of Bordetella pertussis in Bordetella parapertussis Infection”, Eur. J. Clin Microbiol Infect Dis. 10:793-798, 1996) and swine (Kobisch et al., “Identification of a 68-Kilodalton Outer Membrane Protein as the Major Protective Antigen of Bordetella bronchiseptica by Using Specific-Pathogen-Free Piglets”, Infect. Immun. 58(2):352-357, 1990).
Prior to the present invention, there had been no showing that a Bordetella bronchiseptica p68 antigen can be a safe and effective vaccine in dogs. Therefore, there is a need to develop a Bordetella bronchiseptica vaccine containing a p68 antigen that is suitable for canine use. It would be even more advantageous if such a Bordetella bronchiseptica p68 vaccine is safe for administration to puppies and provides a long-term protection.
CD is a universal, high-mortality viral disease with variable manifestations. Approximately 50% of nonvaccinated, nonimmune dogs infected with CD virus develop clinical signs, and approximately 90% of those dogs die.
Infectious canine hepatitis or ICH, caused by canine adenovirus type 1 (CAV-1), is a universal, sometimes fatal, viral disease of dogs characterized by hepatic and generalized endothelial lesions. CAV-2 causes respiratory disease, which, in severe cases, may include pneumonia and bronchopneumonia.
CPI is a common viral upper respiratory disease. Uncomplicated CPI may be mild or subclinical, with signs becoming more severe if concurrent infection with other respiratory pathogens exists.
CPV infection results in enteric disease characterized by sudden onset of vomiting and diarrhea, often hemorrhagic. Leukopenia commonly accompanies clinical signs. Susceptible dogs of any age can be affected, but mortality is greatest in puppies. In puppies 4-12 weeks of age CPV may occasionally cause myocarditis that can result in acute heart failure after a brief and inconspicuous illness. Following infection many dogs are refractory to the disease for a year or more. Similarly, seropositive bitches may transfer to their puppies CPV antibodies which can interfere with active immunization of the puppies through 16 weeks of age.
CCV also causes enteric disease in susceptible dogs of all ages worldwide. Highly contagious, the virus is transmitted primarily through direct contact with infectious feces, and may cause clinical enteritis within 1-4 days after exposure. Severity of disease may be exacerbated by concurrent infection with other agents. Primary signs of CCV infection include anorexia, vomiting, and diarrhea. Frequency of vomiting usually diminishes within a day or 2 after onset of diarrhea, but diarrhea may linger through the course of infection, and stools occasionally may contain streaks of blood. With CCV infection most dogs remain afebrile and leukopenia is not observed in uncomplicated cases.
Leptospirosis occurs in dogs of all ages, with a wide range of clinical signs and chronic nephritis generally following acute infection. Infection with L. canicola and L. icterohaemorrhagiae cannot be differentiated clinically.
Prior to the present invention, there have been no effective combination vaccines that protect dogs against Bordetella bronchiseptica and one or more of other canine pathogens such as CD virus, CAV-2, CPI virus, CPV, CCV, and a Leptospira species such as L. bratislava, L. canicola, L. grippotyphosa, L. icterohaemorrhagiae and L. pomona. A problem in developing combination vaccines involves efficacy interference, namely a failure of one or more antigens in a combination composition to maintain or achieve efficacy because of the presence of the other antigens in the composition. This is believed to be a result of interference with an antigen in the composition administered to a host, e.g., a dog, in the immunological, antigenic, antibody or protective response such antigen induced in the host because of the other antigens present in the composition. However, for other hosts, such as cats, combination vaccines are known. It is believed that efficacy interference in dogs is due to some peculiarity of the canine biological system, or due to the reaction of the antigens with the canine biological system.
There is a need, therefore, to develop a combination vaccine suitable for administration to dogs against Bordetella bronchiseptica and one or more other canine pathogens, which does not exhibit efficacy interference in canines. It would be even more advantageous if such a combination vaccine is safe for administration to puppies and provides long-term protection.